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Titolo:
Kinetic and equilibrium analyses of [I-123]epidepride binding to striatal and extrastriatal dopamine D-2 receptors
Autore:
Fujita, M; Seibyl, JP; Verhoeff, NPLG; Ichise, M; Baldwin, RM; Zoghbi, SS; Burger, C; Staley, JK; Rajeevan, N; Charney, DS; Innis, RB;
Indirizzi:
Yale Univ, Sch Med, VA Connecticut 116A2, Dept Psychiat, W Haven, CT 06516USA Yale Univ W Haven CT USA 06516 116A2, Dept Psychiat, W Haven, CT 06516USA Yale Univ, Dept Diagnost Radiol, W Haven, CT 06516 USA Yale Univ W Haven CT USA 06516 ept Diagnost Radiol, W Haven, CT 06516 USA Yale Univ, Dept Pharmacol, W Haven, CT 06516 USA Yale Univ W Haven CT USA06516 niv, Dept Pharmacol, W Haven, CT 06516 USA Mt Sinai Hosp, Dept Nucl Med, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp Toronto ON Canada M5G 1X5 Med, Toronto, ON M5G 1X5, Canada Univ Zurich Hosp, Dept Radiol, Div Nucl Med, CH-8091 Zurich, Switzerland Univ Zurich Hosp Zurich Switzerland CH-8091 CH-8091 Zurich, Switzerland
Titolo Testata:
SYNAPSE
fascicolo: 4, volume: 34, anno: 1999,
pagine: 290 - 304
SICI:
0887-4476(199912)34:4<290:KAEAO[>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; HUMAN-BRAIN; I-123 EPIDEPRIDE; PHARMACOLOGICAL CHARACTERIZATION; CEREBRAL-CORTEX; D2 RECEPTORS; BETA-CIT; PET; MODEL; PHARMACOKINETICS;
Keywords:
lipophilic metabolites; SPECT; compartment modeling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Fujita, M Yale Univ, Sch Med, VA Connecticut 116A2, Dept Psychiat, 950 Campbell Ave,W Haven, CT 06516 USA Yale Univ 950 Campbell Ave W Haven CT USA 06516 en, CT 06516 USA
Citazione:
M. Fujita et al., "Kinetic and equilibrium analyses of [I-123]epidepride binding to striatal and extrastriatal dopamine D-2 receptors", SYNAPSE, 34(4), 1999, pp. 290-304

Abstract

Quantitative SPECT measures of dopamine D-2 like receptors with [I-123] epidepride is complicated by its high affinity and lipophilic metabolites. The purpose of this study was to use both parent (P) and lipophilic metabolites (M) as input functions in a kinetic paradigm and in comparison to the results of equilibrium studies. Kinetic studies on eleven healthy human subjects, ages 32 +/- 10 were performed following i.v. injection of similar to 370 MBq of [I-123]epidepride. Images were acquired for 13.5 +/- 1.0 hours. Equilibrium studies were done on seven of eleven subjects with a bolus injection of similar to 140 MBq, bolus/infusion ratio of 10 hours, and infusion for 30-32 hours. High (striatum) and low (temporal cortex) density regions were studied. Two (P and M) and one (P) input function models were applied in the kinetic studies. In receptor-rich regions, the distribution volumes in nondisplaceable compartments were fixed to those in cerebellum. In addition, in the two input function model, K-1(P)/K-1(M) was fixed to the valuesin the cerebellum. The one input function model provided V-3' values (=f(1).B-max'/K-D) which were consistent with those obtained in equilibrium studies in both receptor-rich regions, while the two input function model provided consistent values only in striatum. Poor identifiability of the rate constants of metabolites seemed to be the source of errors in the two input function model. These results suggest that correct V-3' values can be obtained with the one input function model both in high- and low-density regions. (C) 1999 Wiley-Liss, Inc.

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Documento generato il 17/01/20 alle ore 20:15:49